Mucoprotective effects of Saikosaponin-A in 5-fluorouracil-induced intestinal mucositis in mice model
5-Fluorouracil (5-FU)-induced intestinal mucositis (IM) is one of the most common oncological problem. It involves serious clinical consequences such as diarrhea, erythematous lesions of mucosa, and eventually development of ulcers accompanied by severe pain. The aim of the present study was to demo...
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| Veröffentlicht in: | Life sciences (1973) 2019-12, Vol.239, p.116888, Article 116888 |
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| creator | Ali, Jawad Khan, Ashraf Ullah Shah, Fawad Ali Ali, Hussain Islam, Salman Ul Kim, Yeong Shik Khan, Salman |
| description | 5-Fluorouracil (5-FU)-induced intestinal mucositis (IM) is one of the most common oncological problem. It involves serious clinical consequences such as diarrhea, erythematous lesions of mucosa, and eventually development of ulcers accompanied by severe pain. The aim of the present study was to demonstrate the mucoprotective effects of Saikosaponin-A in 5-FU-induced intestinal mucositis in mice. Mucositis was induced in BALB/c mice by intraperitoneal injection of 5-FU (50 mg/kg/day) for three consecutive days and IM was assessed by both behavioral and histochemical analysis. While, Saikosaponin-A (1, 5, 10 mg/kg/day) was administered 1 h before 5-FU injection for consecutive seven days. Pre-treatment of Saikosaponin-A significantly ameliorated the severity of mucositis reflected as food intake, body weight loss, severity of diarrhea and mortality rate in a dose depended manner as compared to mice treated with 5-FU. Moreover, histopathological analysis furthered reinforced the mucoprotective potential of Saikosaponin-A against 5-FU-induced intestinal abnormalities referred as villus atrophy, mitotic crypt stem cells damage, inflammatory cells infiltration, vacuolization and edema. Furthermore, Saikosaponin-A administration strongly inhibited pro-inflammatory mediators (TNF-α, COX-2, IL-1β and IL-6) and apoptotic markers (p-JNK, Casp-3). Saikosaponin-A pre-treatment significantly reduced the production of nitric oxide (NO) in intestinal tissue, inhibited acetic acid-induced Evans blue vascular permeability. The Siaikosaponin-A treatment markedly enhanced the anti-oxidants enzymes (Nrf2, HO-1, SOD, GSH, GST and Catalase), while decreased the oxidative stress markers i.e. Malonaldehde (MDA). Hence, these data suggest that Saikosaponin-A maybe a potential candidate for the treatment of chemotherapy-induced intestinal mucositis. |
| doi_str_mv | 10.1016/j.lfs.2019.116888 |
| format | Article |
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It involves serious clinical consequences such as diarrhea, erythematous lesions of mucosa, and eventually development of ulcers accompanied by severe pain. The aim of the present study was to demonstrate the mucoprotective effects of Saikosaponin-A in 5-FU-induced intestinal mucositis in mice. Mucositis was induced in BALB/c mice by intraperitoneal injection of 5-FU (50 mg/kg/day) for three consecutive days and IM was assessed by both behavioral and histochemical analysis. While, Saikosaponin-A (1, 5, 10 mg/kg/day) was administered 1 h before 5-FU injection for consecutive seven days. Pre-treatment of Saikosaponin-A significantly ameliorated the severity of mucositis reflected as food intake, body weight loss, severity of diarrhea and mortality rate in a dose depended manner as compared to mice treated with 5-FU. Moreover, histopathological analysis furthered reinforced the mucoprotective potential of Saikosaponin-A against 5-FU-induced intestinal abnormalities referred as villus atrophy, mitotic crypt stem cells damage, inflammatory cells infiltration, vacuolization and edema. Furthermore, Saikosaponin-A administration strongly inhibited pro-inflammatory mediators (TNF-α, COX-2, IL-1β and IL-6) and apoptotic markers (p-JNK, Casp-3). Saikosaponin-A pre-treatment significantly reduced the production of nitric oxide (NO) in intestinal tissue, inhibited acetic acid-induced Evans blue vascular permeability. The Siaikosaponin-A treatment markedly enhanced the anti-oxidants enzymes (Nrf2, HO-1, SOD, GSH, GST and Catalase), while decreased the oxidative stress markers i.e. Malonaldehde (MDA). Hence, these data suggest that Saikosaponin-A maybe a potential candidate for the treatment of chemotherapy-induced intestinal mucositis.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2019.116888</identifier><identifier>PMID: 31639401</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>5-Flourouracil ; 5-Fluorouracil ; Abnormalities ; Acetic acid ; Animals ; Antimetabolites, Antineoplastic - pharmacology ; Antioxidants ; Antioxidants - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Atrophy ; Body weight ; Body weight loss ; Catalase ; Chemotherapy ; Cyclooxygenase-2 ; Cytokines ; Diarrhea ; Diarrhea - chemically induced ; Disease Models, Animal ; Dosage ; Edema ; Fluorouracil - pharmacology ; Food intake ; Histochemical analysis ; Inflammation ; Injection ; Interleukin 6 ; Intestinal Mucosa - drug effects ; Intestinal Mucosa - pathology ; Intestinal mucositis ; Intestine ; Intestines - drug effects ; Male ; Markers ; Mice ; Mice, Inbred BALB C ; Mucosa ; Mucositis ; Mucositis - drug therapy ; Mucositis - metabolism ; Nitric oxide ; Oleanolic Acid - analogs & derivatives ; Oleanolic Acid - metabolism ; Oleanolic Acid - pharmacology ; Oxidants ; Oxidative stress ; Oxidizing agents ; Pain ; Permeability ; Pretreatment ; Saikosaponin-A ; Saponins - metabolism ; Saponins - pharmacology ; Stem cells ; Ulcers ; Villus ; Weight loss</subject><ispartof>Life sciences (1973), 2019-12, Vol.239, p.116888, Article 116888</ispartof><rights>2019 Elsevier Inc.</rights><rights>Copyright © 2019 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier BV Dec 15, 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c348t-485065b99871db6d2a5576c275ddeac095aa63a02b2fdbf19ec12e951f7859943</citedby><cites>FETCH-LOGICAL-c348t-485065b99871db6d2a5576c275ddeac095aa63a02b2fdbf19ec12e951f7859943</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S002432051930815X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31639401$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ali, Jawad</creatorcontrib><creatorcontrib>Khan, Ashraf Ullah</creatorcontrib><creatorcontrib>Shah, Fawad Ali</creatorcontrib><creatorcontrib>Ali, Hussain</creatorcontrib><creatorcontrib>Islam, Salman Ul</creatorcontrib><creatorcontrib>Kim, Yeong Shik</creatorcontrib><creatorcontrib>Khan, Salman</creatorcontrib><title>Mucoprotective effects of Saikosaponin-A in 5-fluorouracil-induced intestinal mucositis in mice model</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>5-Fluorouracil (5-FU)-induced intestinal mucositis (IM) is one of the most common oncological problem. It involves serious clinical consequences such as diarrhea, erythematous lesions of mucosa, and eventually development of ulcers accompanied by severe pain. The aim of the present study was to demonstrate the mucoprotective effects of Saikosaponin-A in 5-FU-induced intestinal mucositis in mice. Mucositis was induced in BALB/c mice by intraperitoneal injection of 5-FU (50 mg/kg/day) for three consecutive days and IM was assessed by both behavioral and histochemical analysis. While, Saikosaponin-A (1, 5, 10 mg/kg/day) was administered 1 h before 5-FU injection for consecutive seven days. Pre-treatment of Saikosaponin-A significantly ameliorated the severity of mucositis reflected as food intake, body weight loss, severity of diarrhea and mortality rate in a dose depended manner as compared to mice treated with 5-FU. Moreover, histopathological analysis furthered reinforced the mucoprotective potential of Saikosaponin-A against 5-FU-induced intestinal abnormalities referred as villus atrophy, mitotic crypt stem cells damage, inflammatory cells infiltration, vacuolization and edema. Furthermore, Saikosaponin-A administration strongly inhibited pro-inflammatory mediators (TNF-α, COX-2, IL-1β and IL-6) and apoptotic markers (p-JNK, Casp-3). Saikosaponin-A pre-treatment significantly reduced the production of nitric oxide (NO) in intestinal tissue, inhibited acetic acid-induced Evans blue vascular permeability. The Siaikosaponin-A treatment markedly enhanced the anti-oxidants enzymes (Nrf2, HO-1, SOD, GSH, GST and Catalase), while decreased the oxidative stress markers i.e. Malonaldehde (MDA). Hence, these data suggest that Saikosaponin-A maybe a potential candidate for the treatment of chemotherapy-induced intestinal mucositis.</description><subject>5-Flourouracil</subject><subject>5-Fluorouracil</subject><subject>Abnormalities</subject><subject>Acetic acid</subject><subject>Animals</subject><subject>Antimetabolites, Antineoplastic - pharmacology</subject><subject>Antioxidants</subject><subject>Antioxidants - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Atrophy</subject><subject>Body weight</subject><subject>Body weight loss</subject><subject>Catalase</subject><subject>Chemotherapy</subject><subject>Cyclooxygenase-2</subject><subject>Cytokines</subject><subject>Diarrhea</subject><subject>Diarrhea - chemically induced</subject><subject>Disease Models, Animal</subject><subject>Dosage</subject><subject>Edema</subject><subject>Fluorouracil - pharmacology</subject><subject>Food intake</subject><subject>Histochemical analysis</subject><subject>Inflammation</subject><subject>Injection</subject><subject>Interleukin 6</subject><subject>Intestinal Mucosa - drug effects</subject><subject>Intestinal Mucosa - pathology</subject><subject>Intestinal mucositis</subject><subject>Intestine</subject><subject>Intestines - drug effects</subject><subject>Male</subject><subject>Markers</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mucosa</subject><subject>Mucositis</subject><subject>Mucositis - drug therapy</subject><subject>Mucositis - metabolism</subject><subject>Nitric oxide</subject><subject>Oleanolic Acid - analogs & derivatives</subject><subject>Oleanolic Acid - metabolism</subject><subject>Oleanolic Acid - pharmacology</subject><subject>Oxidants</subject><subject>Oxidative stress</subject><subject>Oxidizing agents</subject><subject>Pain</subject><subject>Permeability</subject><subject>Pretreatment</subject><subject>Saikosaponin-A</subject><subject>Saponins - metabolism</subject><subject>Saponins - pharmacology</subject><subject>Stem cells</subject><subject>Ulcers</subject><subject>Villus</subject><subject>Weight loss</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLxDAUhYMozjj6A9xIwXVrHk3b4GoQXzDiQl2HNLmBjG0zJu2A_94MM7p0dS_ccw_nfAhdElwQTKqbddHZWFBMREFI1TTNEZqTphY5rhg5RnOMaZkzivkMncW4xhhzXrNTNGOkYqLEZI7gZdJ-E_wIenRbyMDatMXM2-xNuU8f1cYPbsiXmRsynttu8sFPQWnX5W4wkwaTLiPE0Q2qy_rkFt3o4k7eOw1Z7w105-jEqi7CxWEu0MfD_fvdU756fXy-W65yzcpmzMuG44q3QjQ1MW1lqEp5K01rbgwojQVXqmIK05Za01oiQBMKghNbN1yIki3Q9d43NfqaUii5TmFTsCgpY6ky55glFdmrdPAxBrByE1yvwrckWO7AyrVMYOUOrNyDTT9XB-ep7cH8ffySTILbvQBSv62DIKN2MCQ-LiSi0nj3j_0PLeWJZQ</recordid><startdate>20191215</startdate><enddate>20191215</enddate><creator>Ali, Jawad</creator><creator>Khan, Ashraf Ullah</creator><creator>Shah, Fawad Ali</creator><creator>Ali, Hussain</creator><creator>Islam, Salman Ul</creator><creator>Kim, Yeong Shik</creator><creator>Khan, Salman</creator><general>Elsevier Inc</general><general>Elsevier BV</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20191215</creationdate><title>Mucoprotective effects of Saikosaponin-A in 5-fluorouracil-induced intestinal mucositis in mice model</title><author>Ali, Jawad ; Khan, Ashraf Ullah ; Shah, Fawad Ali ; Ali, Hussain ; Islam, Salman Ul ; Kim, Yeong Shik ; Khan, Salman</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c348t-485065b99871db6d2a5576c275ddeac095aa63a02b2fdbf19ec12e951f7859943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>5-Flourouracil</topic><topic>5-Fluorouracil</topic><topic>Abnormalities</topic><topic>Acetic acid</topic><topic>Animals</topic><topic>Antimetabolites, Antineoplastic - pharmacology</topic><topic>Antioxidants</topic><topic>Antioxidants - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Atrophy</topic><topic>Body weight</topic><topic>Body weight loss</topic><topic>Catalase</topic><topic>Chemotherapy</topic><topic>Cyclooxygenase-2</topic><topic>Cytokines</topic><topic>Diarrhea</topic><topic>Diarrhea - chemically induced</topic><topic>Disease Models, Animal</topic><topic>Dosage</topic><topic>Edema</topic><topic>Fluorouracil - pharmacology</topic><topic>Food intake</topic><topic>Histochemical analysis</topic><topic>Inflammation</topic><topic>Injection</topic><topic>Interleukin 6</topic><topic>Intestinal Mucosa - drug effects</topic><topic>Intestinal Mucosa - pathology</topic><topic>Intestinal mucositis</topic><topic>Intestine</topic><topic>Intestines - drug effects</topic><topic>Male</topic><topic>Markers</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mucosa</topic><topic>Mucositis</topic><topic>Mucositis - drug therapy</topic><topic>Mucositis - metabolism</topic><topic>Nitric oxide</topic><topic>Oleanolic Acid - analogs & derivatives</topic><topic>Oleanolic Acid - metabolism</topic><topic>Oleanolic Acid - pharmacology</topic><topic>Oxidants</topic><topic>Oxidative stress</topic><topic>Oxidizing agents</topic><topic>Pain</topic><topic>Permeability</topic><topic>Pretreatment</topic><topic>Saikosaponin-A</topic><topic>Saponins - metabolism</topic><topic>Saponins - pharmacology</topic><topic>Stem cells</topic><topic>Ulcers</topic><topic>Villus</topic><topic>Weight loss</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ali, Jawad</creatorcontrib><creatorcontrib>Khan, Ashraf Ullah</creatorcontrib><creatorcontrib>Shah, Fawad Ali</creatorcontrib><creatorcontrib>Ali, Hussain</creatorcontrib><creatorcontrib>Islam, Salman Ul</creatorcontrib><creatorcontrib>Kim, Yeong Shik</creatorcontrib><creatorcontrib>Khan, Salman</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ali, Jawad</au><au>Khan, Ashraf Ullah</au><au>Shah, Fawad Ali</au><au>Ali, Hussain</au><au>Islam, Salman Ul</au><au>Kim, Yeong Shik</au><au>Khan, Salman</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mucoprotective effects of Saikosaponin-A in 5-fluorouracil-induced intestinal mucositis in mice model</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2019-12-15</date><risdate>2019</risdate><volume>239</volume><spage>116888</spage><pages>116888-</pages><artnum>116888</artnum><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>5-Fluorouracil (5-FU)-induced intestinal mucositis (IM) is one of the most common oncological problem. It involves serious clinical consequences such as diarrhea, erythematous lesions of mucosa, and eventually development of ulcers accompanied by severe pain. The aim of the present study was to demonstrate the mucoprotective effects of Saikosaponin-A in 5-FU-induced intestinal mucositis in mice. Mucositis was induced in BALB/c mice by intraperitoneal injection of 5-FU (50 mg/kg/day) for three consecutive days and IM was assessed by both behavioral and histochemical analysis. While, Saikosaponin-A (1, 5, 10 mg/kg/day) was administered 1 h before 5-FU injection for consecutive seven days. Pre-treatment of Saikosaponin-A significantly ameliorated the severity of mucositis reflected as food intake, body weight loss, severity of diarrhea and mortality rate in a dose depended manner as compared to mice treated with 5-FU. Moreover, histopathological analysis furthered reinforced the mucoprotective potential of Saikosaponin-A against 5-FU-induced intestinal abnormalities referred as villus atrophy, mitotic crypt stem cells damage, inflammatory cells infiltration, vacuolization and edema. Furthermore, Saikosaponin-A administration strongly inhibited pro-inflammatory mediators (TNF-α, COX-2, IL-1β and IL-6) and apoptotic markers (p-JNK, Casp-3). Saikosaponin-A pre-treatment significantly reduced the production of nitric oxide (NO) in intestinal tissue, inhibited acetic acid-induced Evans blue vascular permeability. The Siaikosaponin-A treatment markedly enhanced the anti-oxidants enzymes (Nrf2, HO-1, SOD, GSH, GST and Catalase), while decreased the oxidative stress markers i.e. Malonaldehde (MDA). Hence, these data suggest that Saikosaponin-A maybe a potential candidate for the treatment of chemotherapy-induced intestinal mucositis.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>31639401</pmid><doi>10.1016/j.lfs.2019.116888</doi></addata></record> |
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| subjects | 5-Flourouracil 5-Fluorouracil Abnormalities Acetic acid Animals Antimetabolites, Antineoplastic - pharmacology Antioxidants Antioxidants - pharmacology Apoptosis Apoptosis - drug effects Atrophy Body weight Body weight loss Catalase Chemotherapy Cyclooxygenase-2 Cytokines Diarrhea Diarrhea - chemically induced Disease Models, Animal Dosage Edema Fluorouracil - pharmacology Food intake Histochemical analysis Inflammation Injection Interleukin 6 Intestinal Mucosa - drug effects Intestinal Mucosa - pathology Intestinal mucositis Intestine Intestines - drug effects Male Markers Mice Mice, Inbred BALB C Mucosa Mucositis Mucositis - drug therapy Mucositis - metabolism Nitric oxide Oleanolic Acid - analogs & derivatives Oleanolic Acid - metabolism Oleanolic Acid - pharmacology Oxidants Oxidative stress Oxidizing agents Pain Permeability Pretreatment Saikosaponin-A Saponins - metabolism Saponins - pharmacology Stem cells Ulcers Villus Weight loss |
| title | Mucoprotective effects of Saikosaponin-A in 5-fluorouracil-induced intestinal mucositis in mice model |
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